This application requests continuation of funding for a very successful and well-established post-doctoral training program (dating back to 1991) in Major Psychoses and Translational Clinical Neuroscience. It seeks to integrate training in translational clinical neuroscience with an emphasis on the study of schizophrenia and other major psychoses using a "lifespan trajectory perspective." That is, trainees may study illnesses during their characteristic age of onset, but they may also examine them from the perspectives of neurodevelopmental and/or aging processes. This program in integrative translational clinical neuroscience will place strong emphasis on all three aspects: "integrative," "translational/clinical," and "neuroscience." The ultimate goal is to train a group of young investigators who will combine a high level of sophistication about the complexities of clinical phenomena with a firm grounding in some specific area of neuroscience, such as neuroimaging, cognitive neuroscience, and genetics/genomics/molecular biology. The program supports five trainee slots/year. Trainees remain in the program for a minimum of two years, and many elect to continue their training for a total of three years because of the complexities inherent in doing sophisticated integrative translational clinical neuroscience. The minimum experience required for entry into the program is a doctoral degree (M.D., Ph.D.), but many of our trainees have also completed residency training and have M.D./Ph.D.s. Relevance An integration of basic and clinical science will, we hope, help identify the mechanisms and causes of the major psychoses and to suggest improved methods for treating or preventing them. The disorders studied through this program (schizophrenia, depression, and bipolar illness) are three of the top ten contributors to the "global burden of disease," according to a recent study by the World Health Organization. Thus it is crucial that we train a young generation of investigators who will advance knowledge about these diseases over the coming decades. PUBLIC HEALTH RELEVANCE: The disorders studied through this program (schizophrenia, depression, and bipolar illness) are three of the top ten contributors to the "global burden of disease," according to a recent study by the World Health Organization. Thus it is crucial that we train a young generation of investigators who will advance knowledge about these diseases over the coming decades. 20